The proposed experiments are components of a research effort whose long-term objective is to understand the role played by the spinal cord in the control of voluntary movements of the primate arm. This goal includes a search for therapies or interventions that will overcome the motor deficits associated with spinal cord injury. The proposed study advances these goals by elucidating the functional organization of spinal interneurons controlling forearm movements in the normal, behaving monkey. A thorough understanding of normal spinal function is essential before studies of motor impairment and recovery following injury can be interpreted usefully. The specific aims of the project are: 1. What. is the role of short, premotor, propriospinal interneurons located rostral to the cervical enlargement in the control of primate arm and hand movements? 2. How are motoneuron and interneuron excitability regulated during normal movements by the neuromodulators serotonin and noradrenaline? What is the contribution of inhibition to the recruitment and spatial tuning of motoneurons and interneurons? The activity of cervical interneurons and motoneurons will be recorded during voluntary reaching, isolated wrist movements, and contraction of flexor- and extensor muscles of the wrist in the awake monkey. Initial double-labeling anatomical experiments will guide the search for propriospinal neurons by identifying the location of premotor interneurons in the C3-C4 segments that receive direct input from corticospinal fibers. Inhibitory and neuromodulator inputs to spinal neurons will be manipulated with local iontophoresis of pharmacological agents that activate or block serotonin,, noradrenaline, GABA or glycine receptors. Input and output connections of interneurons will be identified with spike-triggered averages of EMG and natural and electrical stimulation of peripheral afferents and descending pathways. These studies will elucidate the mechanisms by which the excitability of interneurons and motoneurons are controlled during voluntary movements and lay the foundation for future studies on the mechanisms of motor dysfunction and recovery from injury.